Eosinophilic esophagitis (EE) is characterized by infiltration of the esophagus with eosinophils (1). EE has become increasingly prevalent based on studies in the United States, Switzerland, and Australia (2). For example, 35-fold increase from 2 cases in 1994 to 72 cases in 2003 at The Children's Hospital of Philadelphia (3).
The symptoms of EE have been described as symptoms suggestive of gastroesophageal reflux, which do not respond to gastroesophageal reflux disease (GERD) medications. Other symptoms of EE include dysphagia especially in young adults and failure to thrive in infants (4). The natural history is unknown, but several studies suggest potential progression of untreated disease. Noel et al (5) in a retrospective study of age versus chief complaint found feeding difficulties in the youngest children (median age 2.0 years), vomiting in older children (median age 8.1 years), abdominal pain in adolescents (median age 12.0 years), and dysphagia (mean age 13.4 years) and food impaction (median age 16.8 years) in adults. One possible analysis of this retrospective data is a gradual progression and potential worsening of symptoms from feeding difficulties in infants to strictures and food impaction in adults as a natural history of untreated disease. In the adult population, Straumann et al (6) found no remission in disease in their 11-year follow-up of 30 adults.
The cause of EE is related to allergy. The majority of patients have evidence of food and aeroallergen hypersensitivity, as defined by skin prick test responses, RAST results, or both; however, only a minority have a history of food anaphylaxis, indicating distinct mechanisms compared with classical IgE-mediated mast cell/basophil activation. The immune mechanisms involved in EE are still unclear. It has been established that IL5 and eotaxin enhance the migration of eosinophils to the gut mucosa. Thus, the immune responses in EE are characterized by enhanced production of Th2-associated cytokines in response to both food and environmental allergens. EE and atopic dermatitis (AD) share common features, including eosinophil infiltration, eosinophil degranulation, and squamous epithelial cell hyperplasia, suggesting that common pathogenetic mechanisms may be operational.
EE is defined by the occurrence of high levels of eosinophils (>20-24 eosinophils/high-powered field) in the esophageal mucosa associated with an extensive epithelial hyperplasia. Eosinophils are located both in the proximal and distal esophagus. In addition, esophageal tissues from patients with EE demonstrate thickened mucosa with basal layer hyperplasia and papillary lengthening. EE has been associated with esophageal dismotility, and the cause of the motor disturbances is unclear, but eosinophil activation and degranulation has been postulated as a possible cause. Radiographic and endoscopic studies have shown many findings, including strictures, mucosal rings, ulcerations, whitish papules, and polyps.
The assessment of EE includes an extended allergy evaluation looking for food and aeroallergen sensitization either by means of skin prick tests or RASTs and the exclusion of GERD, as well as other causes of eosinophils in the esophagus. A recent study has suggested that evaluation of food protein sensitization by means of delayed skin patch testing increases the identification of food allergy compared with skin prick testing alone. Of note, the presence of GERD does not exclude the diagnosis of EE or food allergy, demonstrating the importance of a food allergy evaluation in these patients.
The most common foods identified in EE population by the use of prick skin test and atopy patch test are milk, egg, wheat, soja and peanuts.
The most common aero-allergens involved in the EE onset are pollens and House Dust Mite (HDM).
A trial of specific food antigen avoidance is often indicated for patients with atopic EE, and if unsatisfactory or practically difficult (when patients are sensitized to many allergens), a diet consisting of an elemental formula is advocated. Interestingly, it has been shown that an elemental diet frequently improves symptoms and reduces the number of eosinophils in the esophageal biopsy specimens in patients with primary EE (allergic or nonallergic subtypes). Patients on elemental diets frequently require placement of a gastrostomy tube to achieve adequate caloric support. Glucocorticoids (systemic or topical) have also been used with satisfactory results. Systemic steroids are used for acute exacerbations, whereas topical steroids are used to provide long-term control. In a noncontrolled open-label study, topical fluticasone has been shown to decrease levels of eosinophils and CD8+ cells in the proximal and distal esophagus. However, it has been reported that some patients treated with topical fluticasone had esophageal candidiasis.
It appears that EE requires prolonged treatment similar to that for allergic asthma. Although the natural history of EE has not been extensively followed, it is not uncommon for children with EE to have a parent with a long-standing history of esophageal strictures. In fact, in some cases, examination of esophageal biopsy slides from such parents reveals the long-standing presence of EE. Thus, it is likely that chronic EE, if left untreated, can develop into progressive esophageal scaring and dysfunction. The risk for having Barrett's esophagitis, especially in patients with coexisting EE and GERD, has not been determined but is certainly of concern. Additionally, patients with EE are at increased risk for development of other focus of digestive diseases, and thus routine surveillance of the entire gastrointestinal tract by endoscopy is warranted.
Thus, EE is a severe esophageal disease occurring with increasing frequency in children, adolescents and young adults. It is currently treated by food avoidance and corticoids.
Despite the promising results reported with subcutaneous immunotherapy (SCIT), this method is no longer used in food allergy due to the high level of serious side effects or adverse events (AEs). Authors now favor the oral route, i.e., specific oral tolerance induction (SOTI) or oral immunotherapy (OIT), using increasing oral doses and variable time schedules (from one week to at least 1 year or more) or the sublingual technique (SLIT). These methods are promising and their efficacy has been already established. However, in EE, oral route has not been tested. In addition, it could cause a worsening of the EE due to the contact of the esophageal mucosa with the allergen.
Consequently, there is a need for a new method for EE treatment which is safe, efficient and well tolerated by patients.